Summary

Anoro Ellipta is a combination inhaler containing umeclidinium bromide (a long-acting muscarinic antagonist [LAMA]) and vilanterol (a long-acting beta2 agonist [LABA]). Umeclidinium/vilanterol is the first LAMA/LABA combination inhaler available in the UK for the treatment of COPD. It is licensed as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. The combination inhaler has been compared in randomised controlled trials (RCTs) with its individual components, tiotropium monotherapy and placebo. Studies suggest that there are benefits for forced expired volume in 1 second (FEV1) with the umeclidinium/vilanterol combination inhaler. However, the clinical relevance of these benefits is unclear. There is limited evidence on patient-orientated outcomes such as shortness of breath, quality of life outcomes or exacerbation rates.

The summary of product characteristics (SPC) states that cardiovascular effects, such as cardiac arrhythmias, atrial fibrillation and tachycardia, may be seen after the administration of muscarinic receptor antagonists and sympathomimetics, including umeclidinium/vilanterol.

The SPC states that umeclidinium/vilanterol should be used with caution in people with severe cardiovascular disease. In addition, it states that consistent with its antimuscarinic activity, umeclidinium/vilanterol should be used with caution in people with urinary retention or with narrow-angle glaucoma.

Umeclidinium/vilanterol is available as a dry powder multi-dose inhaler, which may be more convenient for some people than using 2 separate inhalers (LAMA plus LABA as single component inhalers).

Once daily dosing.

Individual patient assessment is needed when choosing an inhaler device.

Resource implications

The cost of Anoro Ellipta is £32.50 for 30 days' supply.

The cost of 2 separate inhalers (currently available LAMA plus LABA as single component inhalers) ranges from approximately £39.38 to £64.13 for 30 days' supply (depending on the LAMA and LABA used and device).

Introduction and current guidance

The NICE guideline on chronic obstructive pulmonary disease (COPD) states that COPD is characterised by airflow obstruction that is usually progressive and not fully reversible; it is predominantly caused by smoking. The guideline makes several recommendations about inhaled treatments for managing stable COPD, which are relevant to the likely place in therapy of umeclidinium/vilanterol (Anoro Ellipta: a long-acting muscarinic antagonist [LAMA] and long-acting beta2 agonist [LABA] combination inhaler).See the NICE guideline or the NICE pathway on COPD for full details.

Product overview

Anoro Ellipta is a multi-dose, dry powder combination inhaler containing a LAMA and a LABA. It is licensed as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. The recommended dose is 1 inhalation once a day. Each delivered dose (the dose that leaves the mouthpiece of the inhaler) contains 65 micrograms of umeclidinium bromide, which is equivalent to 55 micrograms of umeclidinium, and 22 micrograms of vilanterol (as trifenatate) (Anoro Ellipta summary of product characteristics).

Evidence review

This evidence summary is based on the best available published evidence. This is 3 RCTs: 2 RCTs reported in the same paper (Decramer et al. 2014) and (Maleki-Yazdi et al. 2014). The 2 RCTs reported in Decramer et al. 2014 compared 2 different doses of umeclidinium/vilanterol with tiotropium alone and either umeclidinium alone or vilanterol alone over 24 weeks. Maleki-Yazdi et al. 2014 compared umeclidinium/vilanterol with tiotropium over 24 weeks. A fourth 24-week RCT is also briefly discussed (Donohue et al. 2013). All of these RCTs have disease-orientated FEV1 primary outcomes.

Decramer et al. 2014: study 1 found that there was a statistically significant improvement in trough FEV1 of 0.090 litres (95% confidence interval [CI] 0.039 to 0.142; p=0.0006) with umeclidinium/vilanterol 62.5/25 micrograms (equivalent to a delivered dose of umeclidinium 55 micrograms plus vilanterol 22 micrograms) compared with both vilanterol 25 micrograms and tiotropium 18 micrograms (equivalent to a delivered dose of 10 micrograms). However, the clinical significance of this difference is unclear. In study 2 there was no statistically significant difference between umeclidinium/vilanterol 125/25 micrograms and umeclidinium 125 micrograms for the primary outcome. A step‑down statistical testing procedure was used in this study. Tthe results of all further statistical analyses (which included umeclidinium/vilanterol 62.5/25 micrograms) are described, but are not strictly inferential.

Maleki-Yazdi et al. 2014 found that there was a statistically significant improvement in trough FEV1 of 0.112 litres (95% CI 0.081 to 0.144; p<0.001) with umeclidinium/vilanterol 62.5/25 micrograms compared with tiotropium 18 micrograms.

Decramer et al. 2014 and Maleki-Yazdi et al. 2014 reported patient-orientated additional outcomes such as time to first on-treatment exacerbation, St George's Respiratory Questionnaire (SGRQ) score, rescue salbutamol use and the transition dyspnoea (TDI) score. However, the studies were not powered to detect treatment differences in these endpoints. In Decramer et al. 2014 there was no statistically significant difference between umeclidinium/vilanterol 62.5/25 micrograms and tiotropium, umeclidinium or vilanterol monotherapy for time to first on-treatment exacerbation or TDI score. Study 1 of Decramer et al. 2014 and Maleki-Yazdi et al. 2014 both found a statistically significant reduction from baseline in the mean number of salbutamol puffs per day with umeclidinium/vilanterol compared with tiotropium. However, the clinical significance of these reductions (0.7 and 0.5 puffs per day) is unclear. In Maleki-Yazdi et al. 2014 there was a statistically significant improvement from baseline in the SGRQ total score of −2.10 points with umeclidinium/vilanterol compared with tiotropium. The clinical significance of this is unclear.

Donohue at al. 2013 found that there were statistically significant improvements in trough FEV1 on day 169 with umeclidinium/vilanterol 62.5/25 micrograms of 0.052 litres (95% CI 0.017 to 0.087; p≤0.01) compared with umeclidinium 62.5 micrograms and 0.095 litres (95% CI 0.060 to 0.130; p≤0.001) compared with vilanterol 25 micrograms.

In Donohue et al. 2013, TDI score was included as an efficacy outcome and the study was powered to detect a 1 unit difference between treatments. There was a statistically significant improvement in TDI score at day 168 with umeclidinium/vilanterol 62.5/25 micrograms compared with placebo (1.2 units; 95% CI 0.7 to 1.7; p<0.001). There was no statistically significant difference for TDI score with umeclidinium/vilanterol compared with umeclidinium monotherapy (0.3 units; 95% CI −0.2 to 0.7) or vilanterol monotherapy (0.4 units; 95% CI −1.0 to 0.8).

Umeclidinium/vilanterol has been compared with its individual components and the LAMA, tiotropium. There are no published studies which compare umeclidinium/vilanterol with currently available LAMA and LABA treatment given concomitantly.

The European public assessment report for umeclidinium/vilanterol concluded that the overall safety profile was in line with the safety profile of other LAMAs and LABAs. However, it did highlight that long-term safety data is limited. A long-term 52-week safety study (Donohue et al. 2014) has been published. However this study evaluates umeclidinium/vilanterol 125/25 micrograms and does not include the licensed umeclidinium/vilanterol dose.

Context

Umeclidinium/vilanterol is the first LAMA/LABA combination inhaler available in the UK for the treatment of COPD. Indacaterol/glycopyrronium (Ultibro Breezhaler 85/43 micrograms) was the first combination inhaler containing a LABA and a LAMA to receive a European marketing authorisation for COPD (see the evidence summary on chronic obstructive pulmonary disease: indacaterol/glycopyrronium). However, Ultibro Breezhaler was not available in the UK at the time umeclidinium/vilanterol was launched in June 2014. The manufacturer does not currently have a date for the UK launch of Ultibro Breezhaler (Novartis: personal communication September 2014).

Estimated impact for the NHS

The NICE guideline on COPD recommends that the choice of drug treatment should take into account the person's symptomatic response and preference, and the drug's potential to reduce exacerbations, side effects and costs. The use of dual therapy with a LAMA and LABA may be considered if an inhaled corticosteroid (ICS; as part of combination therapy with a LABA) is declined or not tolerated. NICE developed these recommendations in 2010, which predates the publication of the evidence for the newer LABAs and LAMAs such as vilanterol, indacaterol, olodaterol, glycopyrronium and umeclidinium. The umeclidinium/vilanterol combination inhaler is less expensive than the combined cost of other single-component LAMA or LABA inhalers and may be more convenient for people. However, compared with established drugs such as formoterol, salmeterol and tiotropium, the comparative efficacy and long-term safety of umeclidinium/vilanterol is unclear, particularly in terms of important patient-orientated outcomes such as reducing exacerbations, incidence of pneumonia and overall mortality.

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.